title: Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines.
abstract: BACKGROUND
  Histone deacetylase (HDAC) is well known to be associated with tumorigenesis through epigenetic regulation, and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We examined the therapeutic effects of valproic acid (VPA, a HDACI) with a combination of 5-fluorouracil (5-FU) in vitro.
  
  
  METHODS
  A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. Cell viabilities were evaluated by a cell proliferation assay. We determined the anticancer effects of VPA combined with 5-FU in these cell lines.
  
  
  RESULTS
  Pancreas cancer (SUIT-2): No effect of 5-FU (1.0 µM) was observed, but 17% and 30% of proliferation-inhibitory effects were recognized in a dose of 2.5 or 5.0 µM, respectively. Cell viability was only weakly reduced by VPA (0.5 mM). However, in combination of 5-FU (1.0 µM) with VPA (0.5 mM), 19% of inhibitory effect was observed. Cholangiocarcinoma (HuCCT1): 5-FU (1.0 µM) did not suppress the cell viability, but 5-FU (2.5 µM) suppressed by 23%. VPA (0.5 mM) did not suppress the cell viability, while VPA (1.0 mM) weakly decreased it by 11%. Combination of 5-FU (1.0 µM) and VPA (0.5 mM) markedly reduced the cell viability by 30%.
  
  
  CONCLUSIONS
  VPA augmented the anti-tumor effects of 5-FU in cancer cell lines. Therefore, a combination therapy of 5-FU plus VPA may be a promising therapeutic option for patients with pancreas cancer and cholangiocarcinoma.
authors.affiliation: Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.forename: Tovuu Lkhaguva
authors.initials: TL
authors.lastname: Ochir
authors.forename: Jun
authors.initials: J
authors.lastname: Hanaoka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014635:Valproic Acid / Q000008:administration & dosage
chemical_list: D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D005472:Fluorouracil